SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease.

Sarfo, FS; Phillips, RO; Zhang, J; Abass, MK; Abotsi, J; Amoako, YA; Adu-Sarkodie, Y; Robinson, C; Wansbrough-Jones, MH (2014) Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease. BMC Infectious Diseases, 14 (202). ISSN 1471-2334 https://doi.org/10.1186/1471-2334-14-202
SGUL Authors: Robinson, Clive Wansbrough-Jones, Mark Harding Phillips, Richard

[img]
Preview
["document_typename_application/pdf; charset=binary" not defined] Published Version
Available under License St George's repository terms & conditions.

Download (684kB) | Preview

Abstract

BACKGROUND: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy. METHODS: Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy. RESULTS: Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment. CONCLUSIONS: Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy.

Item Type: Article
Additional Information: © 2014 Sarfo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Adolescent, Adult, Aged, Animals, Anti-Bacterial Agents, Buruli Ulcer, Child, Child, Preschool, Female, Humans, Macrolides, Male, Mass Spectrometry, Mice, Middle Aged, Subcutaneous Tissue, Skin, Tissue Distribution, Young Adult, Mycobacterium ulcerans, Mycolactone, Biomarker, Antibiotic therapy, Prognosis, Treatment response, Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, BURULI ULCER, HOST IMMUNE-RESPONSE, CYTOKINE PRODUCTION, TOXIN, STREPTOMYCIN, MACROLIDE, COMBINATION, EFFICACY, RIFAMPIN, GROWTH, Microbiology, 0605 Microbiology, 1103 Clinical Sciences, 1108 Medical Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: BMC Infectious Diseases
ISSN: 1471-2334
Language: eng
Dates:
DateEvent
15 April 2014Published
PubMed ID: 24731247
Web of Science ID: WOS:000335474200002
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107235
Publisher's version: https://doi.org/10.1186/1471-2334-14-202

Actions (login required)

Edit Item Edit Item